Simplified dosing regimens of teicoplanin for patient groups stratified by renal function and weight using Monte Carlo simulation

Yamada, Takaaki; Nonaka, Toshiharu; Yano, Tomoaki; Kubota, Takeshi; Egashira, Nobuaki; Kawashiri, Takehiro; Oishi, Ryozo

doi:10.1016/j.ijantimicag.2012.05.025

Cited by 17 publications

(17 citation statements)

References 18 publications

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“…The regression analyses showed that renal function is an important consideration for appropriate initial teicoplanin dosing, which is in keeping with the findings of recently published studies (16,27,28). Although the impact of renal function on trough concentrations was stronger at 72 h than at 48 h, the results suggest that in patients with enhanced renal function, achieving target trough concentrations may be difficult unless very high loading doses, such as doses of Ͼ20 mg/kg, are used.…”

Section: Discussionsupporting

confidence: 84%

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Byrne

Roberts

McWhinney

et al. 2017

Antimicrob Agents Chemother

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The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of Ն20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P Ͻ 0.05). For an average hematological malignancy patient (creatinine clearance ϭ 70 ml/ min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)

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Section: Discussionsupporting

confidence: 84%

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Byrne

Roberts

McWhinney

et al. 2017

Antimicrob Agents Chemother

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“…Yamada et al [21] developed a dosing regimen stratified by eGFR designed to achieve the new target C min by Monte Carlo simulation. In patients whose body weights were 50-70 kg, the initial loading dose of 400 mg twice daily for 3 days achieved a median C min of 19 μg/ml in patients with an eGFR of 30-60 ml/min/1.73 m 2 , and 20 μg/ml in those with an eGFR of 15-30 ml/min/1.73 m 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Although various enhanced loading dose regimens to achieve the new target C min have been reported in patients with normal Electronic supplementary material The online version of this article (doi:10.1007/s10096-016-2691-z) contains supplementary material, which is available to authorized users. renal function [9,[13][14][15][16][17][18][19][20][21][22], there are limited data in patients with renal dysfunction [19][20][21][22]. Ueda et al [13] reported that the proportion of patients achieving the target C min of 15 μg/ml was only 20.3 % with the conventional teicoplanin loading regimen in patients with renal dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction

Takesue

Nakajima

Ichiki

et al. 2016

Eur J Clin Microbiol Infect Dis

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We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 μg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 μg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 μg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml. In conclusion, achievement of Cmin of 15-30 μg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.

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“…The success rate for optimal trough concentration was much higher in the group that received individualized loading dose regimens than in the group that received conventional loading dose regimens. In study by Yamada et al [14], simplified dosing regimens stratified by renal function and weight using Monte Carlo simulation based on population pharmacokinetics and observed distribution of patient characteristics were found to be helpful to estimate optimal loading and maintenance doses. These findings suggest that the loading dose is mandatory for optimal drug concentration, and that individual adjustment of initial loading and maintenance doses according to population pharmacokinetics could be potentially useful for rapidly achieving optimum levels of therapeutic drug concentrations.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Drug Concentrations of Teicoplanin in Clinical Settings

Nah

Yeo

et al. 2014

Infect Chemother

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BackgroundTeicoplanin is a glycopeptide antibiotic that is widely used in clinical practice for the treatment of infections caused by drug-resistant Gram-positive bacteria. The aim of this study was to analyze plasma teicoplanin concentrations to determine the percentage of patients in whom therapeutic concentrations of teicoplanin were achieved in clinical practice.Materials and MethodsThe plasma teicoplanin concentrations of hospitalized patients receiving treatment at a teaching hospital were retrospectively analyzed. The target level was defined as a plasma teicoplanin concentration of 10 mg/L or greater, since this was generally regarded as the lower limit of the optimal concentration range required for the effective treatment of a majority of infections.ResultsPatients with sub-optimal (< 10 mg/L) plasma teicoplanin concentrations constituted nearly half of the total study population. The majority of these patients received the recommended loading dose, which were three 400 mg doses administered every 12 hours. Sub-group analysis showed a trend that the group receiving loading dose was more likely to reach the optimal teicoplanin concentration.ConclusionsThe data revealed that a significant proportion of patients in clinical practice achieved only sub-optimal teicoplanin concentrations, which emphasizes the importance of the mandatory use of loading dose and routine therapeutic drug monitoring. Treatment reassessment and simulation of individual dose regimens may also be necessary to achieve optimal drug concentrations.

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Simplified dosing regimens of teicoplanin for patient groups stratified by renal function and weight using Monte Carlo simulation

Cited by 17 publications

References 18 publications

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy

Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction

Therapeutic Drug Concentrations of Teicoplanin in Clinical Settings

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